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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 8/2009

01-08-2009 | Original Article

Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines

Authors: Adam S. Giermasz, Julie A. Urban, Yutaro Nakamura, Payal Watchmaker, Rachel L. Cumberland, William Gooding, Pawel Kalinski

Published in: Cancer Immunology, Immunotherapy | Issue 8/2009

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Abstract

While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such “DC exhaustion” can be prevented by the presence of IFNγ during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.
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Metadata
Title
Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines
Authors
Adam S. Giermasz
Julie A. Urban
Yutaro Nakamura
Payal Watchmaker
Rachel L. Cumberland
William Gooding
Pawel Kalinski
Publication date
01-08-2009
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 8/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0648-5

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